RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

Defined as achieving donor derived neutrophil count >500/uL by day 42 in young children with leukemia or myelodysplastic syndrome treated with busulfan, melphalan and fludarabine followed by umbilical cord blood transplantation (UCBT) with two partially HLA matched units.

Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.

Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.

Incidence of relapse [ Time Frame: at 1 and 2 years after transplant ] [ Designated as safety issue: No ]

All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days and then discontinued. If the ANC decreases to <1.0 x 10^9/L, G-CSF will be reinstituted.

Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of >200 ng/mL. For children < 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.

Other Name: CSA

Drug: fludarabine phosphate

Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.

Other Name: Fludara

Drug: melphalan

Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.

Other Name: Alkeran

Drug: mycophenolate mofetil

All patients will begin mycophenolate mofetil (MMF) on day -3. Patients <45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).

Other Name: MMF

Procedure: umbilical cord blood transplantation

The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.

Experimental: Single Unit UCB Transplantation

Patients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).

Biological: filgrastim

All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days and then discontinued. If the ANC decreases to <1.0 x 10^9/L, G-CSF will be reinstituted.

Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of >200 ng/mL. For children < 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.

Other Name: CSA

Drug: fludarabine phosphate

Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.

Other Name: Fludara

Drug: melphalan

Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.

Other Name: Alkeran

Drug: mycophenolate mofetil

All patients will begin mycophenolate mofetil (MMF) on day -3. Patients <45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).

Other Name: MMF

Procedure: umbilical cord blood transplantation

The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.

Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT

Evaluate pattern of chimerism after double UCBT

Determine the incidence of platelet engraftment at 1 year after UCBT

Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after UCBT

Evaluate the developmental outcome after UCBT

Transplant Related Objectives

Determine the incidence of chronic GVHD at 1 year after UCBT

Determine the survival and disease free survival at 1 and 2 years after UCBT

Determine the incidence relapse at 1 and 2 years after UCBT

Eligibility

Ages Eligible for Study:

up to 2 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients on this trial will receive two partially HLA matched umbilical cord blood (UCB) units, if available (treatment arm 1). If two units are not available, then single UCB unit transplantation will be allowed (on treatment arm 2).

UCB units will be selected according to the University Of Minnesota UCB Graft Selection Algorithm. The unrelated cord blood donor(s) must be 4-6/6 HLA-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution).

Patients aged ≤ 2 years at diagnosis (not age of transplant) with hematological malignancy as detailed below:

Acute lymphocytic leukemia: high risk CR1 as evidenced by: High-risk cytogenetic: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22); >1 cycle to obtain CR; CR2 or higher; All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.

Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.

Minimal Residual Disease (MRD): Patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy. MRD will be defined by either flow cytometry (>0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (PCR or FISH) or conventional cytogenetics (g-banding).

Recipients must have a Lansky score > or = 50% and have acceptable organ function defined as:

Renal: glomerial filtration rate > 60ml/min/1.73m^2

Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,

Pulmonary function: oxygen saturation >92%

Cardiac: left ventricular ejection fraction > 45%.

Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.

Exclusion Criteria:

Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00357565